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Cis-acting expression quantitative trait loci in mice

  • Author(s): Doss, S
  • Schadt, E E
  • Drake, T A
  • Lusis, Aldons J
  • et al.
Abstract

We previously reported the analysis of genome-wide expression profiles and various diabetes-related traits in a segregating cross between inbred mouse strains C57BL/6J (B6) and DBA/2J (DBA). By considering transcript levels as quantitative traits, we identified several thousand expression quantitative trait loci [eQTL] with LOD score > 4.3. We now experimentally address the problem of multiple comparisons by estimating the fraction of false-positive eQTL that are Under cis-acting regulation. For this, we have Utilized a classic cis-trans test with (B6 x DBA)F-1 rilice to determine the relative levels of transcripts from the B6 and DBA alleles. The results suggest that at least 64% of cis-acting eQTL with LOD > 4.3 are true Positives, while the remaining, 36% could not be confirmed as truly cis-acting. Moreover, we find that > 96% of apparent cis-acting eQTL occur ill regions that do not share SNP haplotypes. Cis-acting eQTL serve as ail important new resource for the identification of positional candidates ill QTL studies ill mice. Also, we Use the analysis of the correlation structures between genotypes, gene expression traits, and phenotypic traits to further characterize genes expressed ill liver that are Under cis-acting control, and highlight the advantages and disadvantages of integrating genetics and gene expression data in segregating populations.

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